The hydrogenolysis of amides to amines under mild reaction conditions represents a challenging chemical transformation and has recently been defined as a high-priority research area of the pharmaceutical industry. Traditionally, stoichiometric amounts of reducing agents, such as LiAlH4, DIBAL, or NaBH4, are required to reduce amides to amines. All of these reducing agents, however, have poor atom economy and produce environmentally dangerous products.
In contrast, elemental hydrogen, the simplest reducing agent, generates only water as a by-product, thus making the reaction more atom economical and environmentally friendly. However, only recently have efficient molecular catalysts been developed for using hydrogen as the reducing agent—paving the way to a more economical, safe, and environmentally benign production of pharmaceuticals.
Despite their development, these molecular catalysts still suffer from various disadvantages, such as the inability to be easily separated and recycled. Moreover, some of them have relatively short lifetimes due to their susceptibility to bimolecular deactivation.
Thus, there is a need in the art to provide alternative and/or improved catalysts and processes for hydrogenolysing amides to form amines and optionally alcohols, particularly ones that do not suffer from one or more of these drawbacks.
The present invention addresses this need as well as others, which will become apparent from the following description and the appended claims.